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. 2009 Oct;297(4):E889-97.
doi: 10.1152/ajpendo.00351.2009. Epub 2009 Aug 4.

Differential effects of insulin deprivation and systemic insulin treatment on plasma protein synthesis in type 1 diabetic people

Abdul Jaleel  1 , Katherine A Klaus, Dawn M Morse, Helen Karakelides, Lawrence E Ward, Brian A Irving, K Sreekumaran Nair
Affiliations

Differential effects of insulin deprivation and systemic insulin treatment on plasma protein synthesis in type 1 diabetic people

Abdul Jaleel et al. Am J Physiol Endocrinol Metab. 2009 Oct.

Abstract

It remains to be determined whether systemic insulin replacement normalizes synthesis rates of different plasma proteins and whether there are differential effects on various plasma proteins. We tested a hypothesis that insulin deprivation differentially affects individual plasma protein synthesis and that systemic insulin treatment may not normalize synthesis of all plasma proteins. We measured synthesis rates of 41 plasma proteins in seven each of type 1 diabetic (T1DM) and nondiabetic participants (ND) using [ring-(13)C(6)]phenylalanine as a tracer. T1DM were studied while on chronic insulin treatment and during 8 h insulin deprivation. Insulin treatment normalized glucose levels, but plasma insulin levels were higher during insulin treatment than during insulin deprivation in T1DM and ND. Individual plasma proteins were purified by affinity chromatography and two-dimensional gel electrophoresis. Only 41 protein gel spots from over 300 were chosen based on their protein homogeneity. Insulin deprivation and hyperglycemia either significantly increased (n = 12) or decreased (n = 12) synthesis rates of 24 of 41 plasma proteins in T1DM compared with ND. Insulin treatment normalized synthesis rates of 13 of these 24 proteins, which were altered during insulin deprivation. However, insulin treatment significantly altered the synthesis of 14 additional proteins. In conclusion, acute insulin deprivation caused both a decrease and increase in synthesis rates of many plasma proteins with various functions. Moreover, chronic systemic insulin treatment not only did not normalize synthesis of all plasma proteins but also altered synthesis of several additional proteins that were unaltered during insulin deprivation.

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Figures

Fig. 1.
Fig. 1.
Schematic representation of study day procedures. I+, with insulin; I−, without insulin; FFM, fat-free mass.
Fig. 2.
Fig. 2.
Electrophoresis separation and purification of individual plasma proteins. Plasma proteins were first fractionated by immunoaffinity chromatography to low abundant and high abundant proteins. Low abundant proteins were separated by 2-dimensional gel electrophoresis (A), and the high abundant proteins were separated by single-dimension gel electrophoresis (B). The gels were stained with silver to visualize protein gel spots/bands. The numbers displayed are gel spots/bands used for isotopic enrichment analysis, and the numbers match the protein serial numbers in Table 2 and Table S1.
Fig. 3.
Fig. 3.
Decline in plasma protein synthesis during insulin deprivation in type 1 diabetes mellitus (T1DM). The fractional synthesis rate (FSR) of 12 plasma proteins decreased during insulin deprivation in T1DM compared with nondiabetic participants. Of the above 12 proteins, the FSR of 8 proteins did not differ between the insulin-treated and insulin-deprived state (A), but the FSR of 4 proteins were increased (B) by insulin treatment compared with insulin deprivation in T1DM. AMBP, α1-microglobulin/bikunin precursor. Data are represented as means ± SE (n = 7 subjects). ‡Significant difference vs. nondiabetic participants. §Significant difference vs. T1DM insulin-deprived state.
fig. 4.
fig. 4.
Elevation in plasma protein synthesis during insulin deprivation in T1DM. FSR of 12 plasma proteins increased during insulin deprivation in T1DM compared with nondiabetic participants. Of the above 12 proteins, the FSR of 9 proteins were decreased (A) by insulin treatment compared with insulin deprivation in T1DM, but the FSR of 3 proteins (B) did not differ between the insulin-treated and insulin-deprived state. Data are represented as means ± SE (n = 7). ‡Significant difference vs. nondiabetic participants. §Significant difference vs. T1DM insulin-deprived state.
Fig. 5.
Fig. 5.
Impact of insulin treatment and alteration of plasma protein synthesis in T1DM. Fifteen plasma proteins are altered in T1DM during insulin treatment compared with nondiabetic participants. FSR of 5 proteins were lower (A) and FSR of 9 proteins were higher (B). Data are represented as means ± SE (n = 7). ‡Significant difference vs. T1DM insulin treated state.
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